Medicament admixing system

ABSTRACT

A system for mixing or reconstituting a drug contained in a first container with a diluent or fluid contained in a second container. The second container has a port docking assembly for engaging the first container. The first container is rotatable and axially slidable within the port docking assembly. The port docking assembly has an actuator to urge a stopper fluidly sealing the first container into the interior of the first container. The port docking assembly further includes a movable plug constructed to fluidly seal the second container in a first, docked position and to provide access to the interior of the second container in a second, activated position, whereby fluid communication between the first and second containers is provided when the first and second containers are in the second, activated position.

TECHNICAL FIELD

The invention relates generally to a system and method for mixing thecontents of two containers, and more particularly to a system for mixingor reconstituting a medicament contained in a first container with adiluent contained in a second container.

BACKGROUND OF THE INVENTION

Medicaments or drugs administered in a health care environment aretypically packaged in vials whose interior is maintained in a sterilecondition. The vials themselves are sealed by a sterile stopper which istypically pierced by a cannula when it is desired to remove themedicament or drug. Several procedures are required to get the drug fromthe vial into the body of a patient. Each procedure potentiallyjeopardizes the sterility of the vial, the stopper or the medicament.Further, if the medicament in a particular vial is a powder or isconcentrated, there is often a need to add diluent to the vial todissolve the powder or to dilute the concentrated medicament solution tothe desired strength. Devices providing separate compartments in asingle container for separately enclosing different components in suchas way that they may be later intermixed are described in various U.S.patents, including U.S. Pat. No. 2,176,923 to Nitardy; U.S. Pat. No.3,290,017 to Davies et al.; and, U.S. Pat. No. 3,532,254 to Burke et al.Additional devices of this type are disclosed in other U.S. patents,including U.S. Pat. No. 4,458,811 to Wilkinson; U.S. Pat. No. 4,610,684to Knox, et al.; U.S. Pat. No. 4,998,671 to Lefheit; U.S. Pat. No.5,102,408 to Hanacher; U.S. Pat. No. 5,176,526 to Barney, et al.; U.S.Pat. No. 5,462,526 to Barney, et al.; U.S. Pat. No. 5,928,213 to Barney,et al.; U.S. Pat. No. 5,944,709 to Barney, et al.; U.S. Pat. No.6,203,535 to Barney, et al.; and U.S. Pat. No. 6,846,305 to Smith, etal.

Additionally, dual compartmented container systems having the means tointermix the contents of the two containers are also known in the art.For example, Hospira, Inc., the assignee of the present invention, ownsnumerous patents relating to such technology, including U.S. Pat. Nos.4,614,267; 4,614,515; 4,757,911; 4,703,864; 4,784,658; 4,784,259;4,948,000; 4,963,441; and, 5,064,059. Such delivery systems aremanufactured and sold by Hospira, Inc. under the ADD-VANTAGE® trademark.

Accordingly, reconstitution systems and systems to intermix the contentsof two containers from outside the container are well known in the art.While such reconstitution systems according to the prior art provide anumber of advantageous features, they nevertheless have certainlimitations. The present invention seeks to overcome certain of theselimitations and other drawbacks of the prior art, and to provide newfeatures not heretofore available. A full discussion of the features andadvantages of the present invention is deferred to the followingdetailed description, which proceeds with reference to the accompanyingdrawings.

SUMMARY OF THE INVENTION

The present invention generally provides a system for mixing orreconstituting a drug contained in a first container with a diluentcontained in a second container. In one embodiment the first containerhas a body cap that engages a port assembly connected to the secondcontainer to provide for fluid communication between a cavity of thefirst container and a cavity of the second container.

According to one embodiment, the first container is a drug container.The drug container has a neck and an opening in the neck leading to acavity. A stopper is positioned within the opening of the firstcontainer to close off access to the cavity of the first container. Thebody cap is positioned around the neck and body portions of thecontainer body. The body cap has a first mating member adapted to bereceived by a second mating member of the second container forconnecting the first container to the second container. In oneembodiment the first mating member comprises a flange extending from thebody cap.

According to another embodiment, the second container is a diluentcontainer, such as an IV bag. The diluent container has a port assemblyextending therefrom. The port assembly is designed to receive the firstcontainer to place the contents of the first container in fluidcommunication with the contents of the second container.

According to another embodiment, the port assembly has a first openingat a proximal end thereof providing access to a cavity of the porthousing, a second opening opposing the first opening, and a moveableplug sealing the second opening. According to another embodiment, theport housing has a second mating member adapted to engage the firstmating member of the first container for connecting the second containerto the first container. In one embodiment the second mating member is aretainer having a plurality of different length tabs to engage the firstcontainer in different axial positions.

According to another embodiment, the first set of tabs are utilized toassist in docking the first container in the port housing, andpreferably preventing the first container from being removed from theport housing following docking, i.e., in a docked, non-activatedposition. In another embodiment, the second set of tabs is utilized toassist in maintaining the first container in an activated position.

According to another embodiment, the stopper transitions from a firstposition within the opening of the neck of the container body, to asecond position within the cavity of the container body. When thestopper is in the second position medicament can flow through theopening in the first container

According to another embodiment, the port assembly has an integralactuator. The actuator is positioned within the cavity of the porthousing. In one embodiment, the actuator has a proximal end, a distalend, and a central cavity. In another embodiment the actuator iscomprised of a plurality of axial sidewall members with axial gapsbetween the sidewall members.

According to another embodiment, a system for mixing a medicament in afirst container with a sterile fluid in a second container is provided.The system comprises an activation collar connected to the firstcontainer.

According to another embodiment, the first container has a recessedtrack on an outer surface thereof, and the activation collar has aprotrusion that mates with the track. The geometry of the track dictatesallowable movement of the first container.

According to another embodiment, a visual indicator is provided on theouter surface of the first container. The visual indicator is generallyvisible when the first container is in the first or docked position.However, the visual indicator is generally hidden within the portassembly when the first container is in the second or activatedposition, thereby providing a positive visual indication of activation.

Other features and advantages of the invention will be apparent from thefollowing specification taken in conjunction with the followingdrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

To understand the present invention, it will now be described by way ofexample, with reference to the accompanying drawings in which:

FIG. 1 is a perspective view of one embodiment of the presents inventionin which a first container is docked to a second container and activatedto allow for reconstitution of a drug in the first container with adiluent in the second container, with the system shown in the hangingposition for use;

FIG. 2 is a perspective view of one embodiment of a first container inaccordance with the present invention and a second container inaccordance with the present invention, the second container having adocking port, the first and second containers being depicted prior todocking and activation of the first container to the second container;

FIG. 3 is a perspective exploded view of one embodiment of the dockingassembly for the second container in accordance with the presentinvention;

FIG. 4 is an exploded perspective view of one embodiment of the firstcontainer depicted in FIG. 1;

FIG. 5 is a front elevation view of the first container shown in asimulated docked position;

FIG. 6 is a front elevation view of the first container shown in arotated position prior to final activation;

FIG. 7 is a front elevation view of the first container shown in anactivated position following simulated activation;

FIG. 8 is a cross-sectional view of the upper housing assembly of thefirst container about the center-line thereof;

FIG. 9 is a cross-sectional view about the centerline of the firstcontainer and second container prior to docking of the first container;

FIG. 10 is a cross-sectional view about the centerline of the firstcontainer and second container following docking of the first container(i.e., in the docked position);

FIG. 11 is a cross-sectional view about the centerline of the firstcontainer and second container during activation of the first container;

FIG. 12 is a cross-sectional view about the centerline of the firstcontainer and second container following activation of the firstcontainer; and,

FIG. 13 is a perspective view of a method of utilizing a syringe inconnection with the medicament in the first container.

DETAILED DESCRIPTION

While this invention is susceptible of embodiments in many differentforms, there is shown in the drawings and will herein be described indetail preferred embodiments of the invention with the understandingthat the present disclosure is to be considered as an exemplification ofthe principles of the invention and is not intended to limit the broadaspect of the invention to the embodiments illustrated.

Referring now to the Figures, and specifically to FIGS. 1 and 2, thereis shown a two-part admixing or reconstitution system 410 comprised of afirst container 412 and a second container 414. In one embodiment, thefirst container 412 is a medicament or drug container 412 and ispreferably in the form of a vial with an exterior housing, and thesecond container 414 is a diluent container and is preferably in theform of a flexible bag. In a one embodiment the diluent container 414 isa flexible container formed from first and second opposing sheets offlexible material that are joined and sealed at the edges to provide afluid tight cavity for containing a diluent therein. At one edgethereof, the opposing sheets of the flexible diluent container 414 aresealed around the port housing 482 of the port assembly 418 to fixedlyconnect the port assembly 418 to the second container 414.

The first container 412 has an upper body member 416 or body cap 416that is adapted to mate with a retainer 486 in the port assembly 418 ofthe second container 414, as depicted in FIG. 3. The combination of bodycap 416 and retainer 486 of the port assembly 418 assist in docking thefirst container 412 to the second container 414, and also assist inestablishing a fluid connection between the interiors of first container412 and second container 414 in order to enable mixing of the contentsof the two containers 412, 414. Typically, to mix or reconstitute thedrug in the first container 412, the first container 412 is docked orconnected to the port assembly 418 of the second container 414 as shownin FIG. 10, and then the cavities of each container 412, 414 are placedin fluid communication via an activation process, as shown in FIGS. 1and 11-12, in order to mix the contents of first and second containers412, 414.

As shown in FIG. 4, in one embodiment the first container 412 is a vialcontaining a medicament or drug. The medicament or drug can be in anynumber of different forms, including liquid, gel, or powder (e.g.,lyophilized) forms, or in a combination of any of these known forms. Themedicament or drug is depicted in FIG. 4 as being a powdered orlyophilized drug. In this embodiment the first container 412 ispartially surrounded by a body cap 416, a hanger cap 476 and a label480. Connected to the body cap 416 is a removable top cap 464 and anactivation collar 438. Additionally, as shown in FIG. 8, a seal ring 439is provided. The seal ring 439 connects around the neck area 422 offirst container 412, and is adjacent the interior surface of removabletop cap 464 prior to removal of the top cap 464 from the body cap 416.The seal ring 439 prevents any of the diluent and/or medicament fromescaping out of the fluid flow path between the first container 412 andthe second container 414.

First container 412 can be in the form of a vial can be constructed froma variety of known materials, including glasses, plastics, and any othercommercially acceptable materials. The first container 412 generally hasa body portion 420 and a neck 422 extending therefrom. The neck 422 ofthe first container 412 surrounds an opening 424 leading to an internalcavity 426 that houses the contents, such as a medicament or drug, inthe first container 412. In one embodiment the neck 422 of the firstcontainer 412 also has an outwardly extending annular portion 436adjacent the opening 424 of the first container 412.

A stopper 428 is provided in the opening 424 of the first container 412.Stopper 428 is operable to seal second container 414. The stopper 428closes the opening 424 and prevents the contents in the internal cavity426 from escaping out of the cavity 426 of the first container 412. Thestopper 428 also prevents external components from unintentionallyentering the cavity 426 of the first container 412. The stopper 428 hasa body portion 430 that is configured to be positioned within the neck422 of the first container 412, and a top surface 432 that is outwardlyfacing from the neck 422 of the first container 412 when the stopper 428is in the position shown in FIG. 9. In one embodiment the top surface432 of the stopper 428 has a depression 433 to assist in reducing theforces necessary to transition the stopper 428 to a second positionwithin the first container 412. In an alternate embodiment, there is nodepression 433 in the top surface 432 of the stopper 428. Additionally,in a preferred embodiment the stopper 428 also has a flange 434extending from the body portion 430. The flange 434 is beneficial formaintaining the stopper 428 placement in the first container 412 when asyringe or cannula is inserted through stopper 428 to make solutionadditions and/or to withdraw material from the first container 412, andfor providing an air and/or moisture seal when the first container 412is connected to the port assembly 418 of the second container 414. Inthe embodiment depicted in FIG. 9, an undercut 429 is provided about thecircumference of stopper 428 at the point at which the underside offlange 434 meets the stopper body portion 430. Undercut 429 serves as ahinge or folding point to assist in reducing the stopper push-in force,i.e., the force required to push stopper 428 into the interior of firstcontainer 412 when the system of the present invention is moved to theactivated position. Undercut 429 enables flange 434 to hinge or foldupwardly during activation of the system. For example, in the positionshown in FIG. 9, the flange 434 of the stopper 428 rests on the top ofthe outwardly extending annular portion 436 of the neck 422 of the firstcontainer 412, i.e., flange 434 has been folded upwardly due to theapplication of an inwardly directed activation force. In the depictedembodiments of stopper 428, undercut 429 is in the form of a groovehaving a width in the range of 0.03 inches to 0.1 inches. In analternative embodiment, the width of undercut 429 is in the range of0.04-0.07 inches. It will be appreciated by those of ordinary skill inthe art that the dimension and shape of undercut 429 will vary dependingupon (a) the material from which stopper 428 is constructed; and (b) thetarget force required to push stopper 428 into the interior of firstcontainer 412 when the system of the present invention is activated, asdescribed in detail herein.

Referring to the exploded view and the cross-sectional view of the firstcontainer 412 as shown in FIGS. 4 and 9, in one embodiment the body cap416 is generally positioned around the neck portion 422 and the bodyportion 420 of the first container 412. More specifically, the body cap416 has an internal cavity 456 that houses at least a portion of thebody 420 of the first container 412. The body cap 416 thus generallycovers the upper portion of the first container 412 and assists indocking the first container 412 to the second container 414, as well asassisting in activating the system 410.

As shown in FIGS. 4 and 9, the body cap 416 has a sidewall 442. A track441 is provided in the sidewall 442 of the body cap 416. As explainedherein, the track 441 guides the movement of the first container 412 incombination with the activation collar 438 during the transition of thefirst container 412 from the docked position to the activated position.In the embodiment depicted in FIG. 4, track 441 is an indent or recessin the sidewall 442 of the body cap 416. The track 441 is designed toreceive a protrusion 479 extending from the activation collar 438 suchthat protrusion 479 can move therein. The track 441 has a first verticalportion 443, a horizontal portion 445, and a second vertical portion447. The track 441 also has at least one defeatable stop 449. In oneembodiment a defeatable stop 449 is provided in the first verticalportion 443. In an alternative embodiment, another defeatable stop 449is provided in the horizontal portion 445 of the track 441. Thedefeatable stop 449 operates to preclude movement of the activationcollar 438 by not allowing the protrusion 479 on the inner sidewall ofthe activation collar 438 to pass over the defeatable stop 449 until acertain amount of force is applied, whereupon the stop is “defeated” andfurther movement becomes possible. The first vertical portion 443 of thetrack 441 is relatively short, and is generally provided to allow for asmall amount of movement in overcoming the defeatable stop 449.Conversely, the second vertical portion 447 of the track 441 is longerto allow for complete axial movement of the first container 412 withrespect to the second container 414 which results in activation of thesystem 410, as explained in detail below. The second vertical portion447 of the track 441 has an activation marker 485 which cooperates withthe activation marker 483 to provide a visual indication of properrotational alignment of the first container 412 for activation. Thehorizontal portion 445 of the track 441 joins the first vertical portion443 and the second vertical portion 447 to provide a single continuoustrack. The horizontal portion 445 allows for rotational movement of thebody cap 416 with respect to the activation collar 438 (which ismaintained stationary via its splines 481 as identified herein) suchthat the activation marker 485 on the body cap 416 will align withactivation marker 483 on the activation collar 438 (see FIGS. 4-7). Inan alternative embodiment, the body cap 416 has first and second tracks441 spaced 180° apart on the sidewall 442 of the body cap 416, and theactivation collar 438 has mating first and second protrusions 479 spaced180° apart. In another alternative embodiment, the body cap 416 hasfirst, second, and third tracks 441 spaced 120° apart on the sidewall442 of the body cap 416 and the activation collar 438 has mating first,second, and third protrusions 479 spaced 120° apart.

The body cap 416 also has a first mating member that engages a secondmating member of the port housing assembly 418. In a preferredembodiment the first mating member of the body cap 416, and thus firstcontainer 412, comprises first and second annular flanges 450, 451 thatextend radially outward from a distal portion of the sidewall 442 of thebody cap 416, as shown in FIGS. 4-8. The first annular flange 450 ispositioned adjacent the distal end of the body cap 416, and the secondannular flange 451 is positioned a predetermined distance below thefirst annular flange 450. In one embodiment, the first annular flange450 of the first mating member is utilized to assist in centering thefirst container 412 in the port housing 482 (see FIGS. 9 and 10) anddocking the first container 412 to the port housing 482 in the dockedposition (see FIG. 10). The second annular flange 451 of the firstmating member is utilized to assist in maintaining the first container412 in the fully activated position (see FIG. 12). In the depictedembodiments of the present invention, the first and second annularflanges 450, 451 have circular circumferential perimeters that are sizedand shaped to fit within the opening to the retainer 486 of the porthousing 482, and to engage the tabs 520, 522 of the retainer 486 of theport housing 482. In alternative embodiments, first and second annularflanges 450, 451 have interrupted circumferential perimeters, i.e., oneor more gaps or voids are present about the circumference.

As explained above, the top cap 464 of the body cap 416 is removable. Asshown in FIGS. 4 and 8, the top cap 464 has a pull ring 465 associatedtherewith. The top cap 464 provides an integral cap for the firstcontainer 412 that prevents the first container 412 from being docked tothe second container 414 prior to removal of the top cap 464, and italso protects the first container 412 from any attempted tampering bygenerally providing a protective seal over the opening to the body cap416 to seal the internal cavity 456 of the body cap 416, including allcomponents and surfaces interior of the body cap 416, from the outsideenvironment and to provide sterility to the area in the interior of thebody cap 416. Thus, one cannot access the contents of the firstcontainer 412 when the top cap 464 is still connected to the body cap416. The top cap 464 also has a circumferential rib 467 that protrudesaxially downward into the cavity of the body cap 416. As shown in FIG.8, the circumferential rib 467 engages an annular depression 437 in thetop of the seal ring 439 to assist in properly aligning the firstcontainer 412 in the body cap 416. In one embodiment, the body cap 416and top cap 464 are manufactured integrally from a low densitypolyethylene. It will be appreciated that a variety of materials, andcombinations of materials, can be used in the manufacture of body cap416 and top cap 464. A thin wall 466 joins the top cap 464 to the bodycap 416. The thin wall 466 can be ruptured to disconnect the top cap 464from the body cap 416. To remove the top cap 464, the user pulls on thepull ring 465, which in turn ruptures the thin wall 466 connecting thetop cap 464 to the body cap 416, thereby disconnecting the top cap 464from the remainder of the body cap 416 (see FIG. 9). Because thin wall466 is ruptured in the process of removing top cap 464 from body cap416, top cap 464 cannot be reattached, thus providing evidence ofpossible tampering with the contents of first container 412.

Referring to FIG. 8, the body cap 416 also has first and second ribseals 460. The rib seals 460 are preferably protrusions extendingradially inwardly from the interior surface of the body cap 416 into thecavity 456 of the body cap 416 to engage the first container 412 andprovide a seal against contaminants entering the cavity 456 of the bodycap 416. In one embodiment each rib seal 460 is interrupted atapproximately 180° to allow for venting of the cavity 456, however, theinterruptions of the first rib seal 460 are offset 90° from theinterruptions of the second rib seal 460 to provide an interrupted,tortuous path for the preservation of sterility of the cavity 456 of thebody cap 416 and the contents thereof.

Seal ring 439 is configured to engage the neck area 422 of the firstcontainer 412. As shown in FIG. 8, the seal ring 439 comprises agenerally cylindrical component having a sidewall 453. The sidewall 453has a first flange 455 extending radially outward from the sidewall 453at an upper first end portion thereof, and a second flange 459 extendingradially inward from the sidewall 453 at a lower second end portionthereof The seal ring 439 also has an internal shoulder 463. Theinternal shoulder 463 and the second flange 459 cooperate to create arecess 469 to receive and retain the outwardly extending annular portion436 of the neck 422 of the first container 412. Additionally, the sealring 439 has a series of radially inwardly extending annular ribs 471extending from the sidewall 453 of the seal ring 439 to seal against theneck 422 of the first container 412. As explained above, the seal ring439 also has an annular depression 437 in the top of the seal ring 439to receive the annular rib 467 extending from the top cap 464. Finally,the seal ring 439 has a first opening 473 adjacent the second flange459, through which the vial 412 enters to engage the seal ring 439, anda second opening to provide access to the stopper 428 when the seal ring439 is connected to the first container 412. The seal ring 439 also hasan inner flange 475 extending radially inward and opposing the firstflange 455. The inner flange 475 engages the legs 507 of the plug 489 asis explained herein. In one embodiment the seal ring 439 is made of aplastic material, and preferably a thermoplastic polyester elastomer.Thermoplastic polyester elastomeric materials generally provide theflexibility of rubbers, the strength of plastics and the processibilityof thermoplastics. They can be processed easily by conventionalthermoplastic processes like injection molding, blow molding,calendaring, rotational molding, extrusion and meltcasting.

Referring to FIGS. 4-9, an activation collar 438 is connected to theouter sidewall of the body cap 416. The activation collar 438 incombination with the body cap 416 assist in controlling movement of thefirst container 412 as the first container 412 is docked to the portassembly 418. The activation collar 438 has a cylindrical sidewall 477with a protrusion 479 extending inwardly from the inner surface of thesidewall 477, as discussed above. The protrusion 479 is a mating memberthat mates with the track 441 in the sidewall 442 of the body cap 416.In one embodiment of the present invention, the activation collar 438has first and second protrusions 479 spaced 180° apart. Similarly, thebody cap 416 has first and second tracks 441 spaced 180° apart on thesidewall 442 of the body cap 416. It will be appreciated the number andconfiguration of protrusions 479 and tracks 441 can be varied withoutdeparting from the spirit and scope of the present invention. Theengagement between the protrusions 479 on the activation collar 438 andthe tracks 441 on the body cap 416 maintain the activation collar 438connected to the outer sidewall of the body cap 416, and are explainedin detail herein. Additionally, the protrusion 479 on the activationcollar 438 and the track 441 cooperate as a stop following docking ofthe first container 412 in the port housing 482 of the second container414 to preclude unintentional activation of the first container 412.

The activation collar 438 also has a plurality of splines 481 extendingfrom the sidewall 477 thereof In one embodiment the splines 481 extendfrom an exterior surface of the sidewall 477 of the activation collar438. In one embodiment, the activation collar 438 has 36 splines 481.According, in that embodiment the splines 481 are spaced every 10°.However, it will be appreciated that the number of splines 481 can bevaried. The splines 481 of the activation collar 438 engage a matingprotrusions 519 on the port assembly 418 (see FIG. 9) to precluderotation of the activation collar 438 when the first container 412 isattached or “docked” to the second container 414. Such engagement isexplained in detail herein. In the configuration of the presentinvention wherein 36 splines 481 are provided, the maximum angularrotation required to have the splines 481 of the activation collar 438engage the mating protrusions 519 of the port assembly 418 is 5°.Additionally, in a preferred embodiment, the splines 481 on the outersurface of the activation collar 438 have a chamfered lead-in to assistin mating the splines 438 with the mating protrusions 519 as explainedherein. The activation collar 438 also has an activation marker 483 toprovide a visual indication of proper rotational alignment of theactivation collar 438 with the body cap 416 for activation. In apreferred embodiment the activation collar 438 is made of apolypropylene material. As shown in FIG. 10, the outer surface of thebody cap 416, including the activation collar 438, has a circumferencethat is smaller than the opening to the port housing 482. In thismanner, the body cap 416 secured to the first container 412 can beinserted into the port housing 482 for docking and subsequent activationof the first container 412.

As shown in FIGS. 1, 4, and 9, the first container 412 has a hanger cap476 provided at the distal end of the body portion 420 of the firstcontainer 412. In one embodiment, the hanger cap 476 has a shapegenerally consistent with the shape of the distal end of the bodyportion 420 of first container 412. In the depicted embodiment, thehanger cap 476 has a generally cylindrical shape. The hanger cap 476also has a hingeable connector 478 extending therefrom. As shown in FIG.1, the connector 478 can be pivoted from the lower portion of the hangercap 476 to assist in hanging the reconstitution system 410, such as fromconventional IV pole or other structure configured for holding an IVbag.

Referring now to FIGS. 1, 2, 4-7, and 9, in one embodiment the firstcontainer 412 has a label 480 that connects the body cap 416 to thehanger cap 476, and secures the body cap 416 and the hanger cap 476 onthe first container 412. As shown in FIG. 9, in such an embodiment whenthe body cap 416 and hanger cap 476 are fully seated on the firstcontainer 412, a gap of approximately 0.060″ exists between mating endsof the body cap 416 and the hanger cap 476.

The reconstitution system 410 also has an activation marker 487. In oneembodiment the activation marker 487 is a colored band 487 on the label480 joining the body cap 416 to the hanger cap 476. As explained herein,the activation marker 487 is visible when the first container 412 isdocked to the second container 414 (see FIG. 5), as well as during theprocess of activation (see FIG. 6), however, after full activation hasoccurred the activation marker 487 becomes hidden under the activationcollar 438 (see FIGS. 1 and 7). Accordingly, a positive visualindication that full and complete activation has occurred is providedwhen the activation marker 487 is no longer visible.

Referring now to FIGS. 1-3, the second container 414 has a port assembly418 that is adapted to engage the body cap 416 of the first container412 to dock the first container 412 on the second container 414.Accordingly, one function of the port assembly 418 is as a receiver fordocking the drug vial 412. The port assembly 418 also includes astructure to facilitate fluid communication between the first container412 and the second container 414 for activation, admixing, and/orreconstitution of the medicament in the first container 412.

As shown in FIG. 3, the port assembly 418 generally comprises a porthousing 482, an actuator 484, a plug 489, a retainer 486, a peelablecover 488 and an overcap 490. In the embodiment of the present inventiondepicted in FIG. 3, the retainer 486 of the port assembly 418 is aretainer or docking member 486. Portions of the retainer 486 engage thefirst mating member (i.e., the first and second flanges 450, 451) of thefirst container 412 during docking and activation of the first container412. The peelable cover 488 and overcap 490 assist in maintaining thesterility of the contents of the port assembly 418. Peelable cover 488and overcap 490 also provide evidence of tampering with the contents offirst container 412.

As best shown in FIGS. 3 and 9, the port housing 482 of the portassembly 418 has a first housing portion 492 having a first end 494 anda second end 496. A flange 498 extends radially outwardly from the firstend 494 of the first housing portion 492, and a shoulder 499 extendsradially inwardly from the second end 496 of the first housing portion492. Another housing portion 502 extends from the first housing portion492. In one embodiment, as shown in FIGS. 1 and 9, wherein the secondcontainer 414 is a flexible diluent bag, the second container 414 isfixedly connected to the outer wall of housing portion 502 of the porthousing assembly 418 to connect the port assembly 418 with the interiorcavity 415 of the second container 414. In such an embodiment housingportion 502 preferably has a semi-elliptical outer shape (as depicted inFIG. 3) to assist in sealing the second container 414 to the porthousing 482.

The first housing portion 492 of the port housing 482 has an interiorsurface 504 defining a first cavity 506, and housing portion 502 has aninterior wall 512 defining another cavity or interior bore 514 of theport housing 482. The port housing 482 has an annular recess 513provided adjacent the exit to the bore 514 at the distal end 515 ofhousing portion 502. In the embodiment depicted in FIG. 9, a raised lip517 is provided.

The plug 489 of the port assembly 418 is positioned in the bore 514 ofthe port housing 482. The plug 489 has a seal member 491 positionedwithin or at the end of housing portion 502 to prevent fluid fromescaping into or out of the second container 414 through the inner bore514 of port housing 482. The plug 489 fluidly separates the interiorcavity 415 of the second container 414 from the interior bore 514 of theport housing 482.

The port housing 482 also has an interior seal wall 576 extendingaxially into the first cavity 506 of the first housing portion 492 fromthe shoulder 499 at the second end portion 496 of the first housingportion 492. In one embodiment the interior seal wall 576 is generallycylindrically shaped, and is concentrically positioned with respect tothe interior surface 504 of the first housing portion 492 of the porthousing 482. In a second embodiment, the interior seal wall 576 isslightly tapered. The interior seal wall 576 extends downwardly andcontacts or engages the first flange 455 extending radially outwardlyfrom the sidewall 453 at an upper first end 457 of the seal ring 439during activation of the first container 412. The engagement of theinterior seal wall 576 with the first flange 455 of the seal ring 439during activation of the first container 412 operates as a seal. Asexplained herein, when the first container 412 is transitioned axiallytoward the second container 414 during the activation step, the firstflange 455 of the seal ring 439 will slide on the interior seal wall576, as shown in FIGS. 10-12. A seal is created between the interiorseal wall 576 and the first flange 455 of the seal ring 439.

As explained above, the port assembly 418 has an actuator 484. In oneembodiment, the actuator 484 is integral with the port housing 482. Asshown in FIGS. 3 and 9, the actuator 484 extends axially into the firstcavity 506 of the first housing portion 492 from the shoulder 499 at thesecond end 496 of the first housing portion 492. The actuator 484 isfurther positioned radially inwardly and generally concentrically to theinterior seal wall 576 of the port housing 482. The actuator 484 isformed of a plurality of ribs or sidewall members 501 that extend fromthe shoulder 499 of the port housing 482 and terminate at a bottom 503.In a preferred embodiment, the actuator 484 is comprised of threesidewall members or ribs 501 with axial gaps 505 between each sidewallmember or rib 501. The sidewall members or ribs 501 define a centralcavity 521 of the actuator 484, and the axial gaps 505 provide access tothe central cavity 521. The central cavity 521 ultimately becomes afluid flow path. The outside diameter of the sidewall members or ribs501 approximates the inside diameter of the opening 424 of the firstcontainer 412. The distal end of the sidewall members or ribs 501 can betapered inwardly toward actuator bottom 503. As is explained herein, theactuator 484 is preferably constructed of a relatively rigid material,e.g., a rigid plastic, so that it can be used to displace the stopper428 into the internal cavity 426 of the first container 412 as shown inFIGS. 11-12. The large axial gaps 505 of the actuator 484 facilitatefluid communication with the contents of the first container 412 whenthe actuator 484 is positioned within the opening 424 of the firstcontainer 412. In a preferred embodiment the port housing 482 and itsintegral actuator 484 are made of a polypropylene copolymer.

As explained above, the plug 489 of the port assembly 418 is positionedwithin the bore 514 defined by the interior wall 512 of housing portion502. The plug 489 has an end wall 497 with an annular seal member 491 atthe distal end 493 thereof The seal member 491 surrounds thecircumference of the distal end 493 of the plug 489. An annular rib 495of the seal member 491 engages the annular recess 513 in the porthousing 482 to seal the interior cavity 415 of the second container 414from the interior bore 514 of the port housing 482. The plug 489 alsohas a plurality of legs 507 extending axially away from a main body 509of the plug 489. In a preferred embodiment, the plug 489 has three legs507 as shown in FIGS. 3 and 9. A radial extension 511 is provided at theterminal end of each leg 507. As is explained herein, the radialextensions 511 of the legs 507 are provided to engage the seal ring 439.Finally, a cavity 513 is defined between the legs 507 of the plug 489.The cavity 513 is fully accessible through the gaps between the legs 507of the plug 489 and at the distal open end of the plug 489.

As best shown in FIGS. 3 and 9, the retainer or docking member 486 islocated within the first cavity 506 of the first housing portion 492 ofthe port housing 482. The retainer 486 comprises a body portion having abase 518, a plurality of different length tabs 520, 522 extending fromthe base 518, and a flange 524 extending from a proximal end of theretainer 486. The retainer 486 also has one or more protrusions 519extending from an interior surface of the base 518. The protrusions 519mate with the space between the splines 481 on the outer surface of theactivation collar 438. In one embodiment, the protrusions 519 incombination with the geometry of the base 518 also operate as a stop forthe activation collar 438 when the first container 412 is inserted intothe port assembly 418 (shown in FIG. 10) for docking of the firstcontainer 412 therein. In one embodiment the flange 524 of the retainer486 is fixed to the flange 498 of the port housing 482, e.g., the uppersurface of the flange 524 of the retainer 486 is ultrasonically weldedto the lower surface of the flange 498 of the port housing 482.Accordingly, in such an embodiment the retainer 486 is fixed in the porthousing 482. Retainer 486 and port housing 482 can be formed from asingle piece of material or from multiple components without departingfrom the scope of the present invention.

As shown in FIGS. 3 and 9-12, and explained above, the retainer 486 hasa plurality of tabs 520, 522. In one embodiment, a first set of tabs 520are shorter in height than a second set of tabs 522. In this embodiment,the first set of tabs 520 is utilized to support the first container 412in the docked position as shown in FIG. 10, and the second set of tabs522 is utilized to support the first container 412 in the activatedposition as shown in FIG. 12. Each of the tabs 520 and 522 can include atapered portion at the distal end thereof Retainer 486 can beconstructed of a flexible material, such as plastic, e.g., apolypropylene copolymer, to allow the tabs 520, 522 to be flexed whenthe first container 412 is inserted into the port housing 482, andthereafter allowing tabs 520, 522 to spring back into their originalposition. Accordingly, tabs 520 and 522 allow the first container 412 tobe pushed in a first axial direction toward the second container 414,but resist movement backward in the opposing direction to prevent thefirst container 412 from being removed from engagement with the porthousing 482 following docking and activation of the first container 412.

Referring to FIGS. 9-12, as the first container 412 is inserted into theport housing 482, the first annular flange 450 centers the firstcontainer 412 in the opening at the proximal end the retainer 486 of theport housing 482. As the first container 412 is pushed axially inward,the first annular flange 450 flexes the distal end of the first set oftabs 520 radially outwardly to allow the first annular flange 450 toextend axially inwardly of the tabs 520. When the first annular flange450 is positioned inwardly of the first set of tabs 520, the tabs 520will flex back and return to their original, unflexed positions. In thisposition, as shown in FIG. 10, the annular flange 450 is docked on thefirst set of tabs 520, and the first set of tabs 520 prevent the annularflange 450, and thus the first container 412, from being pulled out ofthe retainer 486. In this way the system prevents first container 412from being “undocked” from second container 414 after the dockingprocess has been completed, thereby minimizing the possibility oftampering and/or the compromising of the sterility of the system.Further, in this position the splines 481 on the activation collar 438engage the protrusions 519 on the retainer 486 to prevent the activationcollar 438, and moreover, the entire first container 412, from rotatingwithin the port housing 482.

After the first container 412 is docked in the port housing 482, thesystem 410 can be activated at any subsequent time. To activate, thefirst container 412 is initially moved axially inwardly toward the porthousing 282, such that the protrusion 479 on the activation collar 438overcomes the defeatable stop 449 (see FIG. 5). Next, the firstcontainer 412 is rotated with respect to the fixed activation collar438, by rotating the first container 412 (see FIG. 6). As explainedabove, movement of the first container 412 is limited to that allowed bythe track 441. After the first container 412 is rotated such that it hasexhausted the possible translation of the protrusion 479 in thehorizontal portion 445 of the track 441, the first container 412 canagain be axially translated toward the second container 414 and furtherwithin the port housing 482 (see FIG. 7).

While the activation step has been identified functionally above, itwill herein be described structurally. As the first container 412 ispushed axially inwardly on the second vertical track portion 447 andinto the first cavity 506 of the port housing 482, the first annularflange 450 will contact the distal end of the second set of tabs 522 andflex the second set of tabs 522 radially outwardly to allow the firstannular flange 450 to extend axially inwardly of the second set of tabs522 (see FIG. 11). This is referred to as the partially activatedposition. To obtain full activation, as shown in FIG. 12, the firstcontainer 412 must be pushed even further axially inwardly on the secondvertical track portion 447 and into the first cavity 506 of the porthousing 482. As shown in FIG. 12, the second annular flange 451 willcontact the distal end of the second set of tabs 522 and flex the secondset of tabs 522 radially outwardly to allow the second annular flange451 to be positioned axially inwardly of the second set of tabs 522.When the second annular flange 451 is positioned inwardly of the secondset of tabs 522, the tabs 522 will flex back and return to an unflexedposition (see FIG. 12). This is referred to as the activated orfully-activated position. In this position, the second annular flange451 is positioned on the second set of tabs 522, and the second set oftabs 522 prevents the second annular flange 451, and thus the firstcontainer 412, from being pulled out of the retainer 482. In thisposition the first container 412 is prevented from further axialmovement toward the second container 414. These features preventintentional tampering as well as other activities that could compromisethe sterility of the contents of first container 412 and secondcontainer 414.

In the embodiment of the present invention shown in FIG. 3, the portassembly 418 also includes a peelable cover 488. The peelable cover 488is positioned on the flange 424 of the retainer 486 connected to theport housing 482 to provide a protective seal over the opening to theport assembly 418 and to seal the interior of the port assembly 418,including all components and surfaces thereof, from the outsideenvironment and to provide sterility to this area. In one embodiment thepeelable cover 488 is made of Tyvek® material (or other known materials)and an appropriate adhesive on one side thereof to facilitate thebonding of peelable cover 488 to retainer 486. Peelable cover 488 canhave one or more tabs or extensions to assist in its removal fromretainer 486. An overcap 490, preferably made of a plastic material, ispreferably constructed to serve as a protector for the peelable cover488. In the embodiment depicted in the attached figures, the overcap 490has a pair of sidewalls and flanges that grasp around the peelable cover488 and onto the flange 498 of the port housing 482 to retain the overcap 490 on the port assembly 418.

In one embodiment of the present invention, in order to mix orreconstitute the contents of the first container 412 with the contentsof the second container 414, the first container 412 is docked orconnected to the port assembly 418 of the second container 414 as shownin FIG. 1. As explained herein, following the docking step, the cavitiesof each container 412, 414 are placed in fluid contact through anactivation process, whereby the contents of the first and secondcontainers 412, 414 can be combined or admixed.

Referring to FIG. 2, the first container 412 can be maintained separatefrom the second container 414 until the drug is requested by a doctor.After a prescription is ordered, a pharmacist or clinician will removethe top cap 464 from the body cap 416 of the first container 412. Thepharmacist or clinician also will remove the over cap 490 and peelablecover 488 from the port housing assembly 418. The first container ordrug vial 412 is now available to be “docked” onto the port assembly418, typically in the pharmacy, by pushing the drug vial 412 into theport assembly 418, as shown in FIGS. 10-12. When the first container 412is moved axially into the port assembly 418, the first annular flange450 contacts the first set of short tabs 520 and flexes the short tabs520 radially outwardly to allow the first flange 550 to move past thetabs 520. After the flange 450 passes the end of the tabs 520, the tabs520 will spring back to their original, unflexed positions, therebylocking first container 412 in the docked position relative to secondcontainer 414. As the flange 450 is forced past the first set of tabs520 the pharmacist will typically hear an audible “pop,” signaling thatthe flange 450 has passed over the tabs 520 and that the vial 412 isdocked and locked in the ready position. Further, in this position, thetabs 520 preclude reverse axial movement and thus do not allow the firstcontainer 412 to be removed from the port housing 482. In addition topreventing possible tampering, the locking of first container 412 in thedocked position ensures that first container 412 is not inadvertentlydisconnected from second container 414 prior to activation. Suchdisconnection could occur during transport of the first container 412and second container 414 (by known means such has by hand, by medicinecart, or by pneumatic system) or during storage of the docked system.

Additionally, during docking the first flange 455 that extends radiallyoutward from the sidewall 453 of the seal ring 439 engages the taperedinterior seal wall 576. Due to the engagement of the flange 455 on thetapered interior seal wall 576, a seal is created between the interiorseal wall 576 and the first flange 455 of the seal ring 439. As shown inFIG. 10, during docking, the bottom 503 of the actuator 484 engages thetop surface 432 of the stopper 428 and exerts a minor force on thestopper 428.

In the docked state, as shown in FIG. 10, the contents of the firstcontainer or drug vial 412 remain separate from the contents of thesecond container or diluent bag 414, however, the first container 412 isfixed to the port assembly 418 and second container 414, and cannot beremoved therefrom without generally destroying various of itscomponents. Thus, at this point the drug vial 412 is mechanicallyconnected to the port assembly 418, but is not fluidly connected to thediluent bag 414. It is understood that in the docked state the contentsof the two containers 412, 414 remain completely separated, and thus thetwo containers 412, 414 can remain in the docked state without admixingfor an extended period typically limited only by the shelf life of thecontents in the two containers 412, 414. In the docked state the stopperis positioned in the opening of the vial, thereby providing a moistureand air barrier for the contents of the first container 412. At any timeafter the drug vial 412 is “docked” on the port assembly 418, a nurse orother clinician can activate the system, thereby enabling mixing orreconstitution of the drug in the first container 412 with the diluentin the second container 414.

To activate the two-part admixing system 410 the clinician will push thefirst container 412 axially toward the second container 414. In thisstep the clinician will have to overcome the defeatable stop 449 bypushing the stop 449 past the protrusion 479 on the inner surface of theactivation collar 438 (see FIG. 5). Next, as shown in FIG. 6, theclinician will have to rotate the first container 412 with respect tothe fixed activation collar 438 and port housing 482. Again, to precludeunintentional activation, in one embodiment the clinician will have toexert enough of a force to push the stop 449 in the horizontal trackportion 445 past the protrusion 479 on the activation collar 438.Finally, as shown in FIGS. 7 and 11-12, the clinician will further pushthe first container 412 axially toward the second container 414 and intothe fully activated position on the second set of tabs 522.

In the final axial activation stage, the seal between the seal member491 of the plug 489 and the port housing 482 is broken as the plug 489is forced partially into the cavity of the second container 414.Additionally, the stopper 428 is forced down the opening 424 in the vial412 and into the inner cavity 426 of the vial 412 as is shown in FIGS.11 and 12 by the proximal end 503 of the actuator 484, thereby creatinga fluid flow path between the first container 412 and the secondcontainer 414.

The opening of the fluid flow path to the second container 414 isdepicted in FIG. 11. When the first container 412 is pushed axiallytoward the second container 414 during activation, the legs 507 pushpast the inner flange 475 of the seal ring 439 and engage the outwardlyextending annular portion 436 of the first container 412. Further, theinner flange 475 captures the legs 507 between the inner flange 475 andthe lip 436 of the vial 412, maintaining the legs 507 therebetween.Accordingly, as the first container 412 is pushed further axially towardthe second container 414 the force will disengage the annular rib 495 ofthe seal member 491 on the plug 489 from the annular recess 513 in theport housing 482, and force the plug 489 into the cavity of the secondcontainer 414, thereby opening the fluid flow path to the secondcontainer 414. As shown in FIG. 11, and as explained above, the firstflange 455 engages the interior seal wall 576 during activation of thefirst container 412. The engagement of the interior seal wall 576 withthe first flange 455 of the seal ring 439 operates to seal the contentsof the second container 414 from escaping out of the port housing 482and past the first container 412.

As shown in the transition from FIG. 11 to FIG. 12, further axialmovement of the first container 412 toward the second container 414operates to transition the stopper 428 into the cavity 426 of the firstcontainer 412, thereby creating a fluid flow between the first container412 and the central cavity 521 of the actuator 484. In one embodiment,the stopper 428 will ultimately be translated entirely through theopening 424 in the first container 412 and will be deposited within thecavity 426 of the first container 412. At this point the cavity 426 ofthe first container 412 is open to the central cavity 521 of theactuator 484. As shown in FIG. 12, the central cavity 521 of theactuator 484 has nearly as large a cross section as the opening 424 tothe first container 412. This assists the reconstitution system 410 bynot restricting the flow of fluid into and out of the first container412.

As the first container 412 is moved to the fully activated position, thesecond annular flange 451 of the body cap 416 moves axially up theretainer 486 toward the second container 414 and past the second set oftabs 522. In this position, as shown in FIG. 12, the second annularflange 451 is positioned on the second set of tabs 522, and the secondset of tabs 522 prevents the second annular flange 451, and thus thefirst container 412, from reverse or proximal axial movement (i.e., theyprevent the first container 412 from being pulled out of or detachedfrom the port housing 482). This is referred to as the activatedposition.

An additional aspect of one embodiment of the two-part admixing system410 is that a visual indication of activation of the system 410 isprovided. As shown in FIGS. 1, 2 and 5-7, in one embodiment anactivation marker 487 is provided. The activation marker 487 may be acolored or printed band 487 on the label 480 joining the body cap 416 tothe hanger cap 476. When the first container 412 is in the dockedposition the activation marker 487 is visible. This indicates to theclinician that the system 410 has not yet been activated. The activationmarker 487 is visible when the first container 412 is docked to thesecond container 414 (see FIG. 5), as well as during the process ofactivation (see FIG. 6). After full activation has occurred, theactivation marker 487 becomes hidden under the activation collar 438(see FIGS. 1 and 7). The inability to see the activation marker 487indicates to the clinician that the admixing system 410 has beenactivated and that fluid flow between the contents of the two containers412, 414 is open. The inability of the clinician to see the activationmarker 487 also indicates to the clinician that the contents ofcontainers 412, 414 are ready for delivery to a patient, i.e., that thecontents of containers 412, 414 have been admixed or diluted fordelivery to the patient.

An additional aspect of one embodiment of the two-part admixing system410, shown in FIG. 13, is that after the top cap 464 is removed from thebody cap 416, the contents of the first container 412 can be accessedwith a syringe to either remove some of the contents thereof, add asmall amount of diluent to the contents thereof, or a combination ofadding contents and removing mixed contents from the first container412. To perform such operations, the clinician may pierce the stopper428 with the needle of a syringe to access the cavity of the firstcontainer 412 as shown in FIG. 13. In this embodiment, first container412 can be used as a standard pharmaceutical vial, i.e., a vial that isaccessed using a hypodermic needle associated with a syringe, and as acomponent of the two-part admixing system 410 of the present invention.Stopper 428 is preferably constructed of a polymeric material that isresistant to coring when a hypodermic syringe needle is pushedtherethrough. The configuration and material of stopper 428 arepreferably selected such that the force required to push a hypodermicsyringe needle there through is ergonomically acceptable to clinicians.In one embodiment of the present invention, the force required to piercestopper 428 with a hypodermic syringe needle is less than 1.5 pounds offorce. In an alternative embodiment, the force required to force ahypodermic syringe needle through stopper 428 is in the range of 0.5-1.0pounds of force. The configuration and material of stopper 428 also arepreferably selected such that the force required to push stopper 428into the interior of first container 412 upon activation of the systemof the present invention is appropriate in view of the mechanicalstrength of the system and ergonomics. It will be appreciated that theforce required to push stopper 428 into the interior of first container412 should be great enough to prevent inadvertent activation whilesimultaneously being small enough to permit both (i) the system of thepresent invention to be constructed of relatively low-cost materials;and (ii) a clinician to readily move the system into its activatedstate. In one embodiment of the present invention, the force required topush stopper 428 into the interior of first container 412 is in therange of 4-20 pounds of force. In a second embodiment, the forcerequired to push stopper 428 into the interior of first container 412 isin the range of 5-15 pounds of force. In a third embodiment, the forcerequired to push stopper 428 into the interior of first container 412 isin the range of 8-13 pounds of force. The material used to constructstopper 428 is preferably a material that is inert to the intendedcontents of first container 412. Where first container 412 is intendedto contain a pharmaceutical product, the material of construction ofstopper 428 is ideally a material that is already approved by regulatoryagencies for use with the pharmaceutical product, thereby minimizing oreliminating the need to undertake extensive compatibility testing toensure that there is no undesirable interaction between thepharmaceutical product and the stopper 428.

In one embodiment, second container 414 is constructed of a non-PVC,DEHP-free material providing a vapor barrier capability that issufficient so as to permit diluent or drug product to be stored thereinwithout the use of an overwrap. For example, second container 414 can beconstructed of the materials utilized by Hospira, Inc., in themanufacture of its VISIV® flex container.

Several alternative embodiments and examples have been described andillustrated herein. A person of ordinary skill in the art will furtherappreciate that any of the embodiments could be provided in anycombination with the other embodiments disclosed herein. Additionally,the terms “first,” “second,” “third,” and “fourth” as used herein areintended for illustrative purposes only and do not limit the embodimentsin any way. Further, the term “plurality” as used herein indicates anynumber greater than one, either disjunctively or conjunctively, asnecessary, up to an infinite number. Additionally, the term “having” asused herein in both the disclosure and claims, is utilized in anopen-ended manner.

It will be understood that the invention may be embodied in otherspecific forms without departing from the spirit or centralcharacteristics thereof. The present examples and embodiments,therefore, are to be considered in all respects as illustrative and notrestrictive, and the invention is not to be limited to the details givenherein. Accordingly, while the specific embodiments have beenillustrated and described, numerous modifications come to mind withoutsignificantly departing from the spirit of the invention and the scopeof protection is only limited by the scope of the accompanying claims.

1. A port assembly for a container storing a sterile fluid to be mixed with a medicament in a vial, said port assembly comprising: a port housing defining a first opening at a proximal end thereof, said first opening providing access to a cavity defined within said port housing, said port housing defining a second opening spaced from said first opening, said second opening providing access to said cavity defined within said port housing, a moveable plug sealing said second opening; an actuator positioned within said cavity of said port housing, said actuator having a proximal end portion and a plurality of sidewall members extending axially from said proximal end portion toward said first opening of the port housing, one or more openings being defined between said sidewall members, said sidewall members have a terminal end spaced from said proximal end portion of said actuator, and a central cavity defined by said sidewall members, said actuator adapted to force a stopper associated with a vial into a vial during an activation step; and a retainer positioned in the cavity defined by said port housing, said retainer having a plurality of retaining tabs, at least one of said plurality of retaining tabs having a first length adapted to retain a vial in a first, docked position, and at least one of said plurality of retaining tabs having a second length adapted to retain a vial in a second, activated position.
 2. A port assembly in accordance with claim 1, wherein said plug has a plurality of legs extending axially toward said first opening, said legs adapted to engage a vial during activation of the vial.
 3. A port assembly in accordance with claim 1, wherein said actuator is integral with said port housing, and wherein said actuator is fixed in place therein.
 4. A port assembly in accordance with claim 1, wherein said port housing has a protrusion extending from an interior wall thereof to engage an activation collar associated with a vial and to prevent relative rotation between an activation collar associated with a vial and said port assembly.
 5. A port assembly in accordance with claim 1, wherein said retainer further comprises a flange defining an opening, said port assembly further comprising a peelable cover sealing said opening defined by said retainer flange.
 6. A port assembly in accordance with claim 5, wherein said port assembly further comprises an overcap removably sealing said opening defined by said retainer flange, said overcap positioned external to said peelable cover.
 7. A port assembly in accordance with claim 1, wherein said port assembly is bonded to a flexible container constructed of a polymeric material, wherein said port assembly provides fluid communication between an exterior and an interior of said flexible container.
 8. A port assembly in accordance with claim 7, wherein said flexible container is constructed of a non-PVC material. 